Project Summary/Abstract Detector for Femtosecond Crystallography Project Summary/Abstract This proposal will enable ground-breaking X-ray Free Electron Laser (XFEL) applications in structural biology by providing a state-of-the-art detector system for the new Macromolecular Femtosecond Crystallography (MFX) beamline at the Linac Coherent Light Source (LCLS). LCLS is the world?s first XFEL and a unique facility in the U.S. MFX opens up the capability to efficiently collect unique and damage-free diffraction data from radiation-sensitive and/or micron-sized crystals of challenging biological systems, including multi-protein complexes and membrane proteins such as GPCRs. This will enable experiments currently not feasible at synchrotrons. MFX will also provide access to a time domain two-to-three orders of magnitude faster than accessible using synchrotrons to investigate biochemical reaction processes. This will enable the determination of catalytically accurate structures of radiation-sensitive metalloenzyme active sites that quickly undergo radiation-induced damage at synchrotrons. The MFX instrument at LCLS is the latest instrument in the LCLS suite and the first purpose- built beamline in response to a growing scientific need and demand. It will be available starting in July 2016 for user experiments and it will house a dedicated crystallography endstation capable of highly automated goniometer-based and injector-based diffraction experiments. Key will be a large detector capable of collecting the maximum information from a single LCLS pulse. This detector is the last missing piece to make the MFX beamline the premier facility for atmospheric pressure structural biology using XFEL beams. In this application, we propose acquiring a Rayonix MX340-HS-C2 detector that provides a fast frame-rate with a larger dynamic range and larger area than any detector currently available at LCLS, and provides a central hole for the direct beam. These features are essential for measuring diffraction data from weakly diffracting crystals and/or from crystals with very large unit cells, typically characteristic of large macromolecular complexes and membrane proteins. The Rayonix detector is capable of operating at 2.5 frames/second at full resolution (7680x7680 44 m pixels) or it may be binned for faster speeds (e.g., 50 frames/second of 221 m pixels). This speed of data collection will greatly increase access to the limited resource of LCLS beamtime for biomedical research and remove beamtime limitations for important projects. The proposed detector will increase the data collection rate at MFX and LCLS up to 50 fold, greatly increasing access to beamtime for important biomedical applications. 1